Studies in the metabolism of the strict anaerobes (Genus <i>Clostridium</i>)

Stickland, L. H.

doi:10.1042/bj0290288

Cited by 79 publications

(26 citation statements)

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“…In several nonpathogenic Clostridium species (e.g., C. sporogenes and C. sticklandii), amino acid metabolism by the Stickland reactions is a primary source of energy when bacteria are grown with amino acids as sole sources of carbon and nitrogen (28)(29)(30)(31). Stickland reactions couple metabolism of pairs of amino acids in which one amino acid, acting as an electron donor, is oxidatively deaminated or decarboxylated and a second amino acid, acting as an electron acceptor, is reduced or reductively deaminated (Fig.…”

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confidence: 99%

Proline-Dependent Regulation of Clostridium difficile Stickland Metabolism

Bouillaut¹,

Self²,

Sonenshein³

2012

Journal of Bacteriology

150

186

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b Clostridium difficile, a proteolytic Gram-positive anaerobe, has emerged as a significant nosocomial pathogen. Stickland fermentation reactions are thought to be important for growth of C. difficile and appear to influence toxin production. In Stickland reactions, pairs of amino acids donate and accept electrons, generating ATP and reducing power in the process. Reduction of the electron acceptors proline and glycine requires the D-proline reductase (PR) and the glycine reductase (GR) enzyme complexes, respectively. Addition of proline in the medium increases the level of PR protein but decreases the level of GR. We report the identification of PrdR, a protein that activates transcription of the PR-encoding genes in the presence of proline and negatively regulates the GR-encoding genes. The results suggest that PrdR is a central metabolism regulator that controls preferential utilization of proline and glycine to produce energy via the Stickland reactions.

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confidence: 99%

Proline-Dependent Regulation of Clostridium difficile Stickland Metabolism

Bouillaut¹,

Self²,

Sonenshein³

2012

Journal of Bacteriology

150

186

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“…However, the primary function of Opp and App in bacteria is to import small, heterogeneous peptides varying from 3 to 20 amino acids relatively nonspecifically as nutrient sources (23)(24)(25)(26)(27). These imported peptides may be utilized as carbon or nitrogen sources and can also serve as the substrates for the generation of ATP in clostridial species via the Stickland reaction (28)(29)(30)(31)(32). The C. difficile genome encodes orthologs of the Opp and App oligopeptide transporter systems and two Rap phosphatase orthologs; however, no clear Phr ortholog is detectable by sequence analysis.…”

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confidence: 99%

Conserved Oligopeptide Permeases Modulate Sporulation Initiation in Clostridium difficile

2014

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The anaerobic gastrointestinal pathogen Clostridium difficile must form a metabolically dormant spore to survive in oxygenic environments and be transmitted from host to host. The regulatory factors by which C. difficile initiates and controls the early stages of sporulation in C. difficile are not highly conserved in other Clostridium or Bacillus species. Here, we investigated the role of two conserved oligopeptide permeases, Opp and App, in the regulation of sporulation in C. difficile. These permeases are known to positively affect sporulation in Bacillus species through the import of sporulation-specific quorum-sensing peptides. In contrast to other spore-forming bacteria, we discovered that inactivating these permeases in C. difficile resulted in the earlier expression of early sporulation genes and increased sporulation in vitro. Furthermore, disruption of opp and app resulted in greater virulence and increased the amounts of spores recovered from feces in the hamster model of C. difficile infection. Our data suggest that Opp and App indirectly inhibit sporulation, likely through the activities of the transcriptional regulator SinR and its inhibitor, SinI. Taken together, these results indicate that the Opp and App transporters serve a different function in controlling sporulation and virulence in C. difficile than in Bacillus subtilis and suggest that nutrient availability plays a significant role in pathogenesis and sporulation in vivo. This study suggests a link between the nutritional status of the environment and sporulation initiation in C. difficile.

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“…Valine is the starting substance for isobutyric acid; leucine is converted to isovaleric acid. (Stickland 1935;Nisman 1954) Due to the fact that the initial concentration of valine and leucine is crucial for the successful, high product yield fermentation, the engaged green biomass has to be optimised in the future. This represents an important milestone on the way to big-scale implementation (Fig.…”

Section: Isobutyric Acid (C4) Isovaleric Acid (C5) Isocaproic Acid mentioning

confidence: 99%

“…This reaction is a particular kind of fermentation of amino acids which is characterised by simultaneous oxidation of one amino acid and reduction of another Heat-resistant spores amino acid (Nisman 1954). The utilisation of just one amino acid is not possible (Stickland 1935). Valine is the starting substance for isobutyric acid; leucine is converted to isovaleric acid.…”

Section: Isobutyric Acid (C4) Isovaleric Acid (C5) Isocaproic Acid mentioning

confidence: 99%